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Title Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus
Author Martin Sturmer, Hans Wilhelm Doerr, Lutz Gurtler
Abstract The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered.
1. Gottlieb MD, SchroV R, Schanker HM, Weissman JD, Fan PT,
Wolf RA, Saxon A (1981) Pneumocystis carinii pneumonia and
mucosal candidiasis in previously healthy homosexual men. N
Engl J Med 305:1425–1431
2. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S,
Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C,
Rozenbaum W, Montagnier L (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deWciency
syndrome (AIDS). Science 220:868–871. doi:10.1126/science.
3. Gallo RC, Sarin PS, Gelmann EP, Robert-GuroV M, Richardson E,
Kalyanaraman VS, Mann D, Sidhu GD, Stahl RE, Zolla-Pazner S,
Leibowitch J, Popovic M (1983) Isolation of human T-cell leukemia virus in acquired immune deWciency syndrome (AIDS).
Science 220:865–867. doi:10.1126/science.6601823
4. Levy JA (2007) HIV and the pathogensis of AIDS, 3rd edn. ASM
Press, Washington DC
5. Gordon S, Pandrea I, Dunham R, Apretei C, Silvestri G (2005) The
call of the wild: what can be learned from studies of SIV infection
in natural hosts. HIV Seq Compendium 2005:2–29. Los Alamos,
New Mexico
6. Barnett SW, Murthy KK, Herndier BG, Levy JA (1994) An AIDS
like condition induced in baboons by HIV-2. Science 266:642–
646. doi:10.1126/science.7939718
7. Onaga R, Kornfeld C, Pandrea I, Estaquier J, Souquière S,
Rouquet P, Apetrei C, Poques P, Müller-Trutwin MC (2002) High
levels of viral replication contrast with only transient changes in
CD4 and CD8 cell numbers during the early phase of experimental infection with simian immunodeWciency virus SIVmnd-1
in Mandrillus sphinx. J Virol 76:10256–10263. doi:10.1128/
8. Van Heuerswyn F, Li Y, Neel C, Bailess E, Keele BF, Liu W, Loul
S, Butel C, Liegeois F, Bienvenue Y, Ngolle EM, Sharp PM, Shaw
GM, Delaporte E, Hahn BH, Peeters M (2006) SIV infection in
wild gorillas. Nature 444:164. doi:10.1038/444164a9. Fleming AP (1988) Seroepidemiology of human immunodeWciency viruses in Africa. Biomed Pharmacother 42:309–320
10. Worobey M, Gemmel M, Teuwen DE, Haselkorn T, Kunstman K,
Bunce M, Muyembe JJ, Kabongo JMM, Kalengayi RM, Van
Marck E, Gilbert MT, Wolinsky SM (2008) Direct evidence of
extensive diversity of HIV-1 in Kinshasa by 1960. Nature
455:661–664. doi:10.1038/nature07390
11. Ndumbe PM, Atchou G, Biwole M, Lobe V, Ayuk-Takem J
(1993) Infections among pygmies in the Eastern province of Cameroon. Med Microbiol Immunol (Berl) 182:281–284. doi:10.1007/
12. Sharp PM, Hahn BH (2008) Prehistory of HIV-1. Nature 455:605–
606. doi:10.1038/455605a
13. Leitner T, Korber B, Daniels M, Calef C, Foley B (2005) HIV-1
subtype and circulating recombinant form (CRF), references
sequences, 2005. HIV Seq Compendium 2005:41–48. Los
Alamos, New Mexico
14. Hemelaar J, Gouws E, Ghys PD, Osmanov S (2006) Global and
regional distribution of HIV-1 genetic subtypes in 2004. AIDS
20:2011–2019. doi:10.1097/01.aids.0000247564.73009.bc
15. Courgnaud V, Abela B, Pourrut X, Mpoudi-Ngolle E, Loul S,
Delaporte E, Peeters M (2003) IdentiWcation of a new simiam
immunodeWciency lineage with a vpu gene present among diVerent cercopithecus monkeys (C. mona, C. cephus, and C. nictitans)
from Cameroon. J Virol 77:12523–12534. doi:10.1128/JVI.77.23.
16. Leitner T, Dazza MC, Ekwalanga M, Apetrei C, Saragosti S
(2007) Sequence diversity among chimpanzee immunodeWciency
viruses (SIVcpz) suggests that SIVcpzPts was derived from SIVcpzPtt through additional recombination events. AIDS Res Hum
Retroviruses 23:1114–1118. doi:10.1089/aid.2007.0071
17. Nerrienet E, Santiago ML, Foupouapuognini Y, Bailes E, Mundy
NI, Njinku B, Kfutwah A, Muller-Trutwin MC, Barre-Sinoussi F,
Shaw GM, Sharp PM, Hahn BH, Ayouba A (2005) Simian immunodeWciency virus infection in wild caught chimpanzees from
Cameroon. J Virol 79:1312–1319. doi:10.1128/JVI.79.2.1312-
18. Van Heuverswyn F, Yingying LI, Bailes E, Neel C, Lafay B, Keele
BF, Shaw KS, Takehisa J, Kraus MH, Loul S, Butel C, Liegeois F,
Yangda B, Sharp PM, Mpoudi-Ngolle E, Delaporte E, Hahn BH,
Peeters M (2007) Genetic diversity and phylogeographic clustering of SIVcpzPtt in wild chimpanzees in Cameroon. Virology
368:155–171. doi:10.1016/j.virol.2007.06.018
19. Quinn T (2008) HIV epidemiology and the eVects of antiviral therapy on long-term consequences. AIDS 22(Suppl 3):S7–S12.
20. Wendler I, Jentsch KD, Schneider J, Hunsmann G (1987) EYcient
replication of HTLV-III and STLV-III mac in human Jurkat cells.
Med Microbiol Immunol (Berl) 176:273–280. doi:10.1007/
21. Nakashima H, Koyanagi Y, Harada S, Yamamoto N (1986) EVect
of HTLV-III on the macromolecular synthesis in HTLV-I carrying
cell line MT-4. Med Microbiol Immunol (Berl) 175:325–334.
22. Owen SM, Yang C, Spira T, Ou CY, Pau CP, Parekh BS, Candal
D, Kuehl D, Kennedy MS, Rudolph D, Low W, Delatorre N,
Masciotra S, Kalish ML, Cowart F, Barnett T, Lal R, McDougal JS
(2008) Alternative algorithm for human immunodeWciency virus
infection diagnosis using tests that are licensed in United States.
J Clin Microbiol 46:1588–1595. doi:10.1128/JCM.02196-07
23. Ayoagi K, Ohue C, Iida K, Kimura T, Tanaka E, Kiyosawa K,
Yagi S (1999) Development of a single and highly sensitive
enzyme immunoassay for hepatitis C virus core antigen. J Clin
Microbiol 37:1802–1808
24. Veillon P, Payan C, Picchio G, Montreuil MM, Guntz P, Lunel F
(2003) Comparative evaluation of the total hepatitis C virus core
antigen, branched-DNA, and Amplicor Monitor assay in determining viremia for patients with chronic hepatitis C during interferon
plus ribavirin combination therapy. J Clin Microbiol 41:3212–
3220. doi:10.1128/JCM.41.7.3212-3220.2003
25. Rouet F, Rouzioux C (2007) The measurement of HIV-1 viral load
in resource limited settings: how and where? Clin Lab (Zaragoza)
26. Schutten M, Peters D, Back NK, Beuselinck K, Foulongne V, Gerreti
AM, Pandiani L, Tiemann C, Niesters HG (2007) Multicenter evaluation of the new Abbott Real Time assays for quantitative detection
of human immunodeWciency virus type 1 and hepatitis C virus RNA.
J Clin Microbiol 45:1712–1717. doi:10.1128/JCM.02385-06
27. Lefrere JJ, Coste J, Defer C, Mercier B, Loisseau P, Vignon D,
Pawlotsky JM, Biagini P, Lerable J, Rouger P, Roudot-Thoraval F,
Ferec C (1999) Screening for HBV, HCV and HIV genomes in
blood donations: shortcomings of pooling revealed by a multicentre study simulating real-time testing. J Virol Methods 80:33–44.
28. OVergeld R, Faensen D, Ritter S, Hamouda O (2005) Human
immunodeWciency virus, hepatitis C and B infections among blood
donors in Germany 2000–2002: risk of virus transmission and the
impact of nucleic acid ampliWcation testing. Euro Surveill 10:8–11
29. Hirsch MS, Günthard HF, Schapiro JM, Brun-Vézinet F, Clotet B,
Hammer SM, Johnson VA, Kunitzkes DR, Mellors JW, Pillay D,
Yeni PG, Jacobsen DM, Richman DD (2008) Antiretroviral drug
resistance testing in adult HIV-1 infection: 2008 recommendation
of the International AIDS society—USA panel. Clin Infect Dis
47:266–285. doi:10.1086/589297
30. Arens M (2001) Clinically relevant sequence-based genotyping of
HBV, HCV, CMV and HIV. J Clin Virol 22:11–29. doi:10.1016/
31. Klug SJ, Molijn A, Schopp B, Holz B, Iftner A, Quint WJF,
Snijders P, Petry KU, Krueger Kjaer S, Munk C, Iftner T (2008)
Comparison of the performance of diVerent HPV genotyping
methods for detection genital HPV types. J Med Virol 80:1264–
1274. doi:10.1002/jmv.21191
32. Cinatl J, Michaelis M, Doerr HW (2007) The threat of avian inXuenza (H5N1). Part III: antiviral therapy. Med Microbiol Immunol
(Berl) 196:203–212. doi:10.1007/s00430-007-0048-z
33. Plantier JC, Dachraoui R, Lemee V, Guedin M, Borsa-Lebas F,
Caron F, Simon F (2005) HIV-1 resistance genotyping on dried
serum spots. AIDS 19:391–397. doi:10.1097/01.aids.0000161768.
34. Ho M (2008) The history of cytomegalovirus and its disease. Med
Microbiol Immunol (Berl) 197:65–73. doi:10.1007/s00430-007-
35. DeClercq E (2007) The design of drugs for HIV and HCV. Nat
Rev Drug Discov 12:1001–1018. doi:10.1038/nrd2424
36. Sloan RD, Ijaz S, Moore PL, Harrison TJ, Teo CG, Tedder RS
(2008) Antiviral resistance mutations potentiate hepatitis B virus
immune evasion through disruption of its surface antigen a determinant. Antivir Ther 13:439–447
37. Menne B, Butter SD, George AL, Tochkov IA, Zhu Y, Xiong S,
Gerin JL, Cote PJ, Tennant BC (2008) Antiviral eVects of lamivudine, emtricitabine, adefovir dipivoxil, and tenofovir disoproxil
fumarate administered orally alone and in combination to
woodchucks with chronic woodchuck  hepatitis virus infection.
Antimicrob Agents Chemother 52:3617–3632. doi:10.1128/
38. Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F,
Houghton M (2007) The way forward in HCV treatment—Wnding
the right path. Nat Rev Drug Discov 12:991–1000. doi:10.1038/
39. Brown TT (2008) Approach to the human immunodeWciency
virus-infected patient with lipodystrophy. J Clin Endocrinol Metab
93:2937–2945. doi:10.1210/jc.2008-101940. Savoia D, Allice T, Tovo PA (2005) Antileishmanial activity of
HIV protease inhibitors. Int J Antimicrob Agents 26:92–94.
41. Trudel N, Garg R, Messier N, Sundar S, Ouellette M, Tremblay
MJ (2008) Intracellular survival of Leishmania species that cause
visceral leishmaniasis is signiWcantly reduced by HIV-1 protease
inhibitors. J Infect Dis 198:1292–1299. doi:10.1086/592280
42. He Y, King MS, Kempf DJ, Lu L, Lim HB, Krishnan P, Kati W,
Middleton T, Molla A (2008) Relative replication capacity and
selective advantage proWles of protease inhibitor-resistant hepatitis C virus (HCV) NS3 protease mutants in the HCV genotype 1b
replicon system. Antimicrob Agents Chemother 52:1101–1110.
43. Forestier N, Reesink HW, Weegink CJ, McNair L, KieVer TL,
Chu HM, Purdy S, Jansen PL, Zeuzem S (2007) Antiviral activity
of telaprevir (VX-950) and peginterferon-2 in patients with hepatitis C. Hepatology 46:640–648. doi:10.1002/hep.21774
44. Soriano V, Peters MG, Zeuzem S (2009) New therapies for hepatitis C virus infection. Clin Infect Dis 48:313–320. doi:10.1086/
45. Grinszteijn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A,
Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD (2007)
Safety and eYcacy of the HIV-1 integrase inhibitor raltegravir
(MK-0518) in treatment-experienced patients with multidrugresistant virus: a phase II randomised controlled trial. Lancet
369:1261–1269. doi:10.1016/S0140-6736(07)60597-2
46. Iwamoto M, Wenning LA, Petry AS, Laethem M, de Smet M, Kost
JT, Breidinger SA, Mangin EC, Azrolan N, Greenberg HE,
Haazen W, Stone JA, Gottesdiener KM, Wagner JA (2008)
Minimal eVects of ritonavir and efavirenz on the pharmacogenetic
of raltegravir. Antimicrob Agents Chemother 52:4338–4343.
47. Hombrouck A, Van Remoortel B, Michiels M, Noppe W, Christ F,
Eneroth A, Sahlberg BL, Benkestock K, Vrang L, Johansson NG,
Barecca ML, De Luca L, Ferro S, Chimirri A, Debyser Z, Witvrouw M (2008) Preclinical evaluation of 1H-benzylindole derivatives as novel human immunodeWciency virus integrase strand
transfer inhibitors. Antimicrob Agents Chemother 52:2861–2869.
48. Malet I, Delelis O, Valentin MA, Montes B, Soulie C, Wirden M,
Tchertanov L, Peytavin G, Reynes J, Mouscadet JF, Katlama C,
Calvez V, Marcelin AG (2008) Mutations associated with failure
of raltegravir treatment aVect integrase sensitivity to the inhibitor
in vitro. Antimicrob Agents Chemother 52:1351–1358.
49. Morozov VA, Morozov AV, Schürmann D, Jessen H, Kücherer C
(2007) Transmembrane protein polymorphism and resistance to
T-20 (Enfurtide, Fuzeon) in HIV-1 infected therapy-naive seroconverters and AIDS patients under HAART-T-20 therapy. Virus
Genes 35:167–174. doi:10.1007/s11262-007-0098-8
50. Mac Arthur RD, Novak RM (2008) Reviews of anti-infective
agents: maraviroc: the Wrst of a new class of antiretroviral agents.
Clin Infect Dis 47:236–241. doi:10.1086/589289
51. Briggs DR, Tuttle DL, Sleasman JW, Goodenow MM (2000)
Envelope V3 amino acid sequence predicts HIV-1 phenotype
(co-receptor usage and tropism for macrophages). AIDS 14:2937–
2939. doi:10.1097/00002030-200012220-00016
52. Lewis M, Simpson P, Fransen S, Huang W, Whitcomb J, Mosley
M, Robertson DL, MansWeld R, Ciaramella G, Westby M (2007)
CXCR4-using virus detected in patients receiving maraviroc in the
Phase III studies MOTIVATE 1 and 2 originates from a pre-existing minority of CXCR4-using virus. Antivir Ther 12:S65
53. Gulick RM, Lalezari J, Goodrich J, Clumeck N, De Jesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Montana JB,
McHale M, Sullivan J, Ridgway C, Felstead S, Dunne MW, van
der Ryst E, Mayer H, MOTIVATE study teams (2008) Maraviroc
for previously treated patients with R5 HIV-1 infection. N Engl J
Med 359:1429–1441. doi:10.1056/NEJMoa0803152
54. Lewis M, Simpson P, Whitcomb J, Li X, Robertson DL, Westby
M (2008) Changes in V3 loop sequence associated with failure of
maraviroc treatment in patients enrolled in the MOTIVATE 1 and
2 trials. In: 15th conference on retroviruses and opportunistic
infections. Boston, 2008. Poster 871
55. Van Baelen K, Salzwedel K, Rondelez E, Van Eygen V, De Vos
S, Verheyen A, Steegen K, Verlinden Y, Allaway GP, Stuyver LJ
(2009) Susceptibility of human immunodeWciency virus type 1 to
the maturation inhibitor Bevirimat is modulated by baseline polymorphisms in gag spacer peptide 1. Antimicrob Agents Chemother
53:2185–2188. doi:10.1128/AAC.01650-08
56. Adamson CS, Waki K, Ablan SD, Salzwedel K, Freed EO (2009)
Impact of human immunodeWciencyvirus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor Bevirimat (PA-457). J Virol 83:4884–4894. doi:10.1128/
57. Borden EC, Sen GC, Uze G, Silverman RH, RansohoV RM, Foster
GR, Stark GR (2007) Interferons at age 50: past, current and future
impact on biomedicine. Nat Rev Drug Discov 12:975–990.
58. Goyal A, Hofmann WP, Hermann E, Traver S, Hissar SS, Aroya
N, Blum HE, Zeuzem S, Sarrazin C, Sarin SK (2007) The hepatitis
C virus NS5A protein and response to interferon  : mutational
analyses in patients with chronic HCV genotype 3a infection from
India. Med Microbiol Immunol (Berl) 196:11–21. doi:10.1007/
Keywords HIV - HBV - HCV - Diagnostics - Therapy
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